Molecular Probes for Imaging Fibrosis and Fibrogenesis

Abstract

Fibrosis, or the accumulation of extracellular matrix molecules that make up scar tissue, is a common result of chronic tissue injury. Advances in the clinical management of fibrotic diseases have been hampered by the low sensitivity and specificity of noninvasive early diagnostic options, lack of surrogate end points for use in clinical trials, and a paucity of noninvasive tools to assess fibrotic disease activity longitudinally. Hence, the development of new methods to image fibrosis and fibrogenesis is a large unmet clinical need. Herein, an overview of recent and selected molecular probes for imaging of fibrosis and fibrogenesis by magnetic resonance imaging, positron emission tomography, and single photon emission computed tomography is provided.

Visualisation of interstitial lung disease by molecular imaging of integrin αvβ3 and somatostatin receptor 2

“…Additional profibrotic molecules which could be of interest for targeted nuclear imaging include extracellular matrix proteins, for example, collagens, fibronectin or fibroblast activation protein 3 52. However, in contrast to our selected imaging targets, radiotracers for these molecules have so far only been validated in animal models53 54 or in human non-ILD conditions 55–57.…”

Molecular imaging of extracellular matrix proteins with targeted probes using magnetic resonance imaging

“…(a) Chemical structures of developed collagen‐targeted probes EP‐3533 and CM‐101 for molecular MR imaging of fibrosis. (b) MR images of a control and fibrotic mouse and its correlation with histological characterization (collagen content), post injection of EP‐3533 in CCl 4 ‐induced liver fibrosis mouse model (Desogere, Montesi, & Caravan, )…”

Improving the reactivity of hydrazine-bearing MRI probes for in vivo imaging of lung fibrogenesis

“…A noninvasive method to identify patients with disease, to identify regions of active disease activity, and/or to identify patients likely to progress rapidly would also have benet in developing new therapeutics for IPF because patients could be better stratied for trial enrolment, and early measures of treatment response may be observed. [10][11][12][13] We are interested in developing molecular magnetic resonance (MR) probes to asses IPF disease activity by targeting biochemical features of active brosis (i.e. brogenesis).…”

“…A noninvasive method to identify patients with disease, to identify regions of active disease activity, and/or to identify patients likely to progress rapidly would also have benefit in developing new therapeutics for IPF because patients could be better stratified for trial enrolment, and early measures of treatment response may be observed. 10 – 13 …”